The latent
membrane protein 1 (LMP1), which is encoded by the Epstein-Barr virus (EBV), is an important oncogenic
protein that is closely related to
carcinogenesis and
metastasis of
nasopharyngeal carcinoma (NPC), a prevalent
cancer in China. We previously reported that the expression of the functional
chemokine receptor CXCR4 is associated with human NPC
metastasis. In this study, we show that LMP1 induces
tyrosine sulfation of CXCR4 through tyrosylprotein sulfotransferase-1 (TPST-1), an
enzyme that is responsible for catalysis of
tyrosine sulfation in vivo, which is likely to contribute to the highly metastatic character of NPC. LMP1 could induce
tyrosine sulfation of CXCR4 and its associated cell motility and invasiveness in a NPC cell culture model. In contrast, the expression of TPST-1
small interfering RNA reversed LMP1-induced
tyrosine sulfation of CXCR4. LMP1 conveys signals through the
epidermal growth factor receptor (EGFR) pathway, and EGFR-targeted
siRNA inhibited the induction of TPST-1 by LMP1. We used a ChIP assay to show that EGFR could bind to the TPST-1 promoter in vivo under the control of LMP1. A reporter gene assay indicated that the activity of the TPST-1 promoter could be suppressed by deleting the binding site between EGFR and TPST-1. Finally, in human NPC tissues, the expression of TPST-1 and LMP1 was directly correlated and clinically, the expression of TPST-1 was associated with
metastasis. These results suggest the up-regulation of TPST-1 and
tyrosine sulfation of CXCR4 by LMP1 might be a potential mechanism contributing to NPC
metastasis.